Induction of heme oxygenase-1 expression in vascular smooth muscle cells. A link to endotoxic shock. 1997

S F Yet, and A Pellacani, and C Patterson, and L Tan, and S C Folta, and L Foster, and W S Lee, and C M Hsieh, and M A Perrella
Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Endotoxic shock is a life-threatening consequence of severe Gram-negative infection characterized by vascular smooth muscle cell relaxation and severe hypotension. The production of nitric oxide (NO), through the inducible NO synthase pathway, has been implicated as a major contributor in this process. We now demonstrate that heme oxygenase (HO), an enzyme that generates carbon monoxide (CO) in the course of heme metabolism, may also be involved in the hemodynamic compromise of endotoxic shock. Inducible HO (HO-1) mRNA levels are dramatically increased in aortic tissue from rats receiving endotoxin, and this increase in vascular HO-1 message is associated with an 8.9-fold increase in HO enzyme activity in vivo. Immunocytochemical staining localizes an increase in HO-1 protein within smooth muscle cells of both large (aorta) and small (arterioles) blood vessels. Furthermore, zinc protoporphyrin IX, an inhibitor of HO activity, abrogates endotoxin-induced hypotension in rats. Studies performed in rat vascular smooth muscle cells in vitro show that the induction of HO-1 mRNA is regulated at the level of gene transcription, and this induction is independent of NO production. Taken together, these studies suggest that the up-regulation of HO-1, and the subsequent production of CO, contributes to the reduction in vascular tone during endotoxic shock.

UI MeSH Term Description Entries
D007022 Hypotension Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients. Blood Pressure, Low,Hypotension, Vascular,Low Blood Pressure,Vascular Hypotension
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011524 Protoporphyrins Porphyrins with four methyl, two vinyl, and two propionic acid side chains attached to the pyrrole rings. Protoporphyrin IX occurs in hemoglobin, myoglobin, and most of the cytochromes.
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006419 Heme Oxygenase (Decyclizing) A mixed function oxidase enzyme which during hemoglobin catabolism catalyzes the degradation of heme to ferrous iron, carbon monoxide and biliverdin in the presence of molecular oxygen and reduced NADPH. The enzyme is induced by metals, particularly cobalt. Haem Oxygenase,Heme Oxygenase,Oxygenase, Haem,Oxygenase, Heme
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012772 Shock, Septic Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status. Endotoxin Shock,Septic Shock,Shock, Endotoxic,Shock, Toxic,Toxic Shock,Toxic Shock Syndrome,Endotoxin Shocks,Shock Syndrome, Toxic,Shock, Endotoxin,Shocks, Endotoxin,Toxic Shock Syndromes

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